NAD+ enhancer modulates mouse colon macrophage shift to an anti-inflammatory character
During colonic inflammation, neutrophils and monocytes can be infiltrated into the colon, although they exist at a low level in steady state. These inflammatory immune cells can be summoned by tissue resident immune competent cells such as macrophages. We further analyzed colonic macrophages in mouse DSS-induced colitis model. Treatment with LMT503 did not alter the percentage or the number of pro-inflammatory CX3CR1intCD206low or anti-inflammatory CX3CR1hiCD206hipopulations (Figure 4a-c). However, TNF-α and iNOS levels were decreased while IL-10 levels were increased following LMT503 treatment in colon and small intestinal macrophages (Figures 4d,e and Figure S1d). Levels of chemokines such as MCP-1/CCL2, KC/CXCL1, and MIP2/CXCL2 were decreased after LMT503 treatment in colon macrophages (Figure 4f), suggesting that colon CX3CR1+macrophages contributed to reduced infiltration of neutrophils and monocytes to the intestine (Figure 3a-d). These data suggest that colon CX3CR1+ macrophage population was not altered after LMT503 treatment, although their character shifted to an anti-inflammatory character to ameliorate DSS-induced colitis.
LMT503 treatment altered macrophages to an anti-inflammatory character to alleviate DSS-induced colitis. The anti-inflammatory environment might arouse susceptibility to infection. To investigate this issue, mice treated with LMT503 were challenged with SalmonellaTyphimurium strain UK-1 at day 13 at the recovery phase of DSS-induced colitis. LMT503 treated group did not show significant body weight loss compared to the vehicle control group (Figure 5a). SalmonellaTyphimurium trafficking to the MLN and spleen did not differ between vehicle control and LMT503 treated groups (Figure 5b). At the recovery phase of colitis, host defense including production of pro-inflammatory cytokines TNF, IL-6, and MCP-1 levels in the colon tissue did not differ significantly after LMT503 treatment (Figure 5c). These data suggest that LMT503 treatment did not increase vulnerability to bacterial infections.